Although the integral role that growth hormone (GH) plays in metabolism and the overall growth of an organism is well established, the specific and varied effects of GH on different cells, tissues and organs are only now becoming recognized and studied. Most notably, the effects of GH on immune system function are still not well appreciated. Analysis of the effects of GH on the immune system will be vital in order to understand its role in normal immunological function, and more significantly to evaluate its potential utility in treating immunologic disease. Understanding the actions of GH on any cell requires characterizing the molecular mechanisms by which the membrane bound receptor for GH is activated and transmits its signal intracellularly. Studying GH receptor signalling in the immune system has a key advantage that serves as the basis for much of this application; namely it should be possible to make mechanistic comparisons between signalling by the GH receptor and signalling by receptors for other cytokines with well-defined roles in immune cell function. The GH receptor has structural similarities to the receptors for cytokines such as the interleukins (ILs) and colony stimulating factors (CSFs) as well as the interferons (IFNs alpha and gamma). In addition, these receptors have a common mechanism of intracellular signalling which involves tyrosine phosphorylation of putatively similar molecules. This provides a framework in which to study the mechanisms of GH receptor activation and signalling. Although the members of this family share common components in their intracellular pathway of signal transduction, they have obvious distinct biological actions which presumably arise from specific differences in these signalling pathways. The IM-9 cell, a human myeloma derived B-lymphocyte line, provides a unique opportunity to unravel the mechanisms underlying this specificity of response in a cell of the immune system. By identifying those signalling steps that are similar as well as elucidating those which are unique will provide insight into the role of GH in immune cell function. The potential mechanisms which confer specificity to the intracellular signalling pathways of the GH and IFNgamma receptors will be analyzed by pursuit of the following Specific Aims: (I) Identification of the tyrosine kinase(s) responsible for the GH activated tyrosine phosphorylations in IM-9 cells and characterization of their specificity regarding activation by the GH receptor. (II) Characterization of the 93 kDa protein which is tyrosine phosphorylated in response to GH and determination of its relationship to the 91 kDa protein which is tyrosine phosphorylated in response to IFNgamma. (III) Determination of the role of tyrosine phosphatase(s) in signalling by the GH receptor in IM-9 cells. (IV) Characterization of the signalling path way of GH activation of MAP kinase in 3T3-F442A cells as an approach to understanding how this signalling path way is different in IM-9 cells.